Host–microbiota interaction induces bi-phasic inflammation and glucose intolerance in mice

Antonio Molinaro, Robert Caesar, Louise Mannerås Holm, Valentina Tremaroli, Patrice D. Cani, Fredrik Bäckhed

The gut microbiota has emerged as an important factor regulating host physiology and metabolism, in particular glucose metabolism and adiposity. Molinaro et al. did a time-resolved study on how colonization of germfree (GF) mice affects kinetics of adiposity and glucose metabolism. They found that colonization resulted in a bi-phasic glucose impairment. The first phase, occurring within 3 days of colonization (early phase) co-occurred with an inflammatory response and was independent of adiposity. The second phase, 14-28 days after colonization (delayed phase), was mostly ascribed to adipose tissue expansion and inflammation.

Objective: Gut microbiota modulates adiposity and glucose metabolism in humans and mice. Here we investigated how colonization of germ-free (GF) mice affects kinetics of adiposity and glucose metabolism.

Methods: Adiposity and glucose metabolism were evaluated at different time points in ex-GF and antibiotic treated mice after colonization with gut microbiota from a conventionally raised (CONV-R) mouse. Mouse physiology, microbiome configuration, serum cytokine levels, and gene expression for inflammatory markers were performed in different tissues.

Results: Colonization resulted in a bi-phasic glucose impairment: the first phase occurring within 3 days of colonization (early phase) and the second 14–28 days after colonization (delayed phase). The early phase co-occurred with an inflammatory response and was independent of adiposity, while the delayed phase was mostly ascribed to adipose tissue expansion and inflammation. Importantly, re-colonization of antibiotic treated mice displays only the delayed phase of glucose impairment and adiposity, suggesting that the early phase may be unique to colonization of the immature GF mice gut.

Conclusions: Our results provide new insights on host–microbiota interaction during colonization of GF mice and the resulting effects on adiposity and glucose metabolism in a time resolved fashion.